Women want to have skin as white and clear as white jade and consider white and clear skin as an important standard of beauty. Thus, whitening agents for treating abnormal skin pigmentation and satisfying the desire for beauty are under active development.
Human skin color is determined by the amounts of melanin, carotene, and hemoglobin. Particularly, melanin has the greatest influence on skin color. Accordingly, control over melanogenesis is considered the most important task for the development of whitening agents.
Melanin is a phenolic polymer that takes the form of a complex of dark pigments and proteins. Melanin is produced from tyrosine through complex processes by the action of tyrosinase present in melanocytes and is a very important and essential substance that protects skin cells against UV-induced damage due to its function of blocking UV light.
Melanin is excessively produced when skin responds to external stimuli, for example, UV light, environmental pollution or stress. Excessive melanin is not released out of the skin but is transferred to keratinocytes and accumulate in the epidermis, causing severe aesthetic problems, such as stains, freckles, and senile lentigo. Excessive melanin promotes skin aging and leads to even skin cancer.
Melanogenesis is largely controlled by two methods well known in the art: a bleaching method for reducing melanin; and a method for inhibiting the activity of tyrosinase, a melanogenesis enzyme. Tocopherol and vitamins are known to be used to reduce melanin. Whitening agents using tocopherol or vitamins are known to be insignificantly effective in skin bleaching. Thus, inhibitors capable of inhibiting the activity of tyrosinase to suppress melanogenesis are attracting attention.
Substances capable of inhibiting the activity of tyrosinase, such as kojic acid and arbutin, hydroquinone, vitamin C (L-Ascorbic acid) and its derivatives, and a variety of plant extracts have been used as whitening ingredients in the cosmetic field. However, these whitening ingredients tend to be degraded and discolored owing to their poor stability in prescription systems, produce off-odors, give unclear efficacy and effectiveness at the biological level, and cause stability problems, which limit their use. Kojic acid chelates copper ions present at active sites of tyrosinase to inhibit the activity of the enzyme but causes stability problems when blended in cosmetic products. Vitamin C and its derivatives are prone to oxidation. Due to their instability, vitamin C and its derivatives are difficult to use as raw materials for cosmetic products. Hydroquinone is very effective in skin whitening but is highly irritant to skin to cause allergies, toxicity to melanocytes, and permanent skin bleaching. In recent years, hydroquinone has been listed as a carcinogenand its use has been forbidden. Only a limited concentration of hydroquinone is currently allowed in most countries around the world. Arbutin is a glucoylated hydroquinone and believed to be have the function of suppressing the synthesis of melanin without toxicity to humans, but still remains evaluation of suitability because of arbutin tends to be partially degraded by skin enzymes. Therefore, there is an urgent need to develop an alterative whitening agent that has improved efficacy even when used in a small amount and is safe without substantially causing side effects.
Breakdown of enzymatic and non-enzymatic antioxidant defense systems of the skin by reactive oxygen results in damage to cell constituents such as proteins, lipids, and DNA (Kor. J. Biotechnol. Bioeng. 2005, 20(1), 40-45). Such damage to cell constituents indicates the incidence of oxidation-associated diseases, i.e. skin aging, wrinkling, and pigmentation.
Scavenging of reactive oxygen species to prevent oxidation derived aging of cells is the most important function of antioxidant activity. The ability of a substance with antioxidant activity to scavenge reactive oxygen species can be associated with the ability of the substance to protect the skin. Melanin is synthesized in melanocytes found in the basal layer of the epidermis. Inflammation-mediating substances caused by reactive oxygen species are known to induce and stimulate melanogenesis in melanocytes. Antioxidants do not exhibit direct whitening effects but can be associated with inhibitory effects on pigmentation.
With this point of view, antioxidants capable of reacting with free radicals are used for the purpose of preventing oxidative cell damage caused by free radicals. Synthetic antioxidants, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate (PG), and tertiarybutyl hydroquinone (TBHQ), are mainly used in foods and pharmaceuticals. However, these antioxidants are known to cause liver hypertrophy or to be involved in carcinogenesis when administered in high doses to experimental animals. In particular, butylated hydroxytoluene is known to increase microsomal enzyme activity in the liver of experimental animals based on many experimental results andthe safety of these phenolic synthetic antioxidants is under debate, with the result that their amountsare legally regulated (Brannen A L, J. Amer. Oil Chem. Soc., 52, pp 59-63, 1975; Ito N et al., J. Natl. Cancer Inst., 70, p 343, 1983; Chan K M et al., J. Food. Sci., 58, ppl-4, 1993). Underthese circumstances, much research has been conducted with high expectations to develop safe and economical natural antioxidants of plant origin that have excellent antioxidant effects (Larson R A, Phytochemistry, 27, pp 969-978, 1988). Along with recent intensive research on natural substances, secondary metabolites present in natural sources have become major concerns as bioactive substances. Particularly, research on antioxidant substances is actively underway. Tocopherols, flavonoids, gossypols, sesamols, oryzanols, and vitamin C are currently known as natural antioxidants (Huson B et al., Food Chem., 19, pp 537-541, 1987; Frankel, E. N. Food Chem., 57, p 51, 1996; Giese J, Food Technol., 5, pp 73-81, 1996; Pszcczola D E, Food Tech., 55, pp 51-59, 2001). Tocopherol and L-ascorbic acid are used as natural antioxidants in preference to others. Tocopherol is highly safe but its ability to prevent oxidation is poor when used alone and its price is high (Halliwell B et al., FASEB J., 2, pp 2867-2870, 1988).
Thus, there is a need to develop an alternative antioxidant substance that can prevent conditions and diseases, including aging, caused by oxidative damage.